The HEROES Trial: Hyperbaric Oxygen Therapy for Endometriosis-Related Pain

Official title

The HEROES Trial: Hyperbaric Oxygen Therapy for Endometriosis-Related Pain: A Prospective Randomized Study

Overview

Endometriosis, is a condition where tissue from the uterus, called endometrium, grows outside of the uterus. This effects up to 10% of women, and can lead to long-lasting, moderate to severe pelvic pain, infertility and other symptoms. This can affect a woman's quality of life (including increased risk of depression and anxiety) and is associated with increased healthcare costs. Current treatments are often limited by serious side effects, and many women resort to surgery. Surgery is also associated with complications and there are long wait times for procedures, sometimes over 3 years. This means that many women continue to suffer from symptoms while they wait for surgery. Therefore, new effective treatments for endometriosis pain are needed. New research suggests that inflammation and stress caused by lack of oxygen in the affected areas may cause endometriosis. Hyperbaric Oxygen Therapy (HBOT), where patients are placed in a small chamber with higher than normal levels of oxygen, suppresses inflammation and promotes tissue healing. Because inflammation is central to this condition, HBOT has emerged as a potential treatment. In this study, the investigators will test if HBOT, in addition to the standard treatments, is more effective at treating endometriosis pain than the standard treatments alone.

Detailed description

Endometriosis is caused when endometrial-like tissue is found outside of the uterus. It predominantly affects women of reproductive age, with an estimated prevalence of 10% worldwide. Chronic pain related to endometriosis is one of the primary manifestations that lead individuals to seek treatment, with many women reporting moderate to severe pain that can have serious consequences for mental health and quality of life.

Current therapeutic approaches for endometriosis include hormonal therapies (e.g. oral contraceptive pills, progestins, and Gonadotropin-Releasing Hormone agonists/antagonists). While these treatments may provide temporary symptom relief, they are often associated with serious side effects and preclude conception during treatment. The efficacy of other medical interventions remains controversial, therefore surgical procedures are often indicated. However, surgery also has associated risks, has long wait times (between 6 months and 3 years), and a considerable percentage of patients experience recurrence of pain following surgical resection.

Pathologically, endometriosis is characterized by angiogenesis, inflammation, and a chronic hypoxic state at the cellular level. Because of this, Hyperbaric Oxygen Therapy (HBOT), which suppresses inflammation and promotes tissue healing, offers promise as a novel therapeutic modality. This is supported by murine models, which demonstrate the ability of HBOT to reduce inflammation and inflammatory cytokines in the context of endometriosis in animals. However, there have not been any human studies investigating the use of HBOT for treatment of endometriosis and related pain.

This study aims to explore HBOT as a treatment for endometriosis related pelvic pain. Specifically, the investigators will test if HBOT, in addition to the standard treatments (e.g. hormonal and non-hormonal medical options), is more effective at treating endometriosis pain than the standard treatments alone.

Interventions

• Device Monoplace Hyperbaric Chamber (Class III medical device)
  Participants in the intervention group will be triaged to the closest hyperbaric facility to their address and treated with 40 HBOTs (2 ATM for 90 mins, scheduled daily from Monday to Friday). As HBOT is not a service currently offered at Sunnybrook Hospital, all HBOT treatments will be provided at three collaborating outpatient facilities, Halton Hyperbaric Unit, Restore Hyperbaric Oxygen \& Medical Centre (CPSO-certified Level-II OHP), and Rouge Valley Hyperbaric Medical Centre. All three faci

Primary outcome measures

• Change in pain symptoms on the NRS [Time frame: At baseline, weekly for the first 8 weeks after enrollment, then at 3/4/5/6 month follow ups]

Secondary outcome measures (4)

• Change in pain frequency [Time frame: At baseline, weekly for the first 8 weeks after enrollment, then at 3/4/5/6 month follow ups]
• Change in opioid consumption [Time frame: At baseline, weekly for the first 8 weeks after enrollment, then at 3/4/5/6 months]
• Participant Quality of Life on the EHP-30 [Time frame: At baseline, and every month for 6 months]
• Participant Quality of Life on the SF-36 [Time frame: At baseline, and every month for 6 months]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years old
• Patients having refractory pelvic pain (NRS≥4) secondary to endometriosis for \>6 months
• May or may not be on traditional multi-modal treatment (pharmacological and/or non-pharmacological)
• On waitlist for surgical treatment

Exclusion criteria

• Patients with chronic pain resulting from disease processes unrelated to the pathophysiology of endometriosis-related symptoms (e.g. irritable bowel syndrome, migraine headache, fibromyalgia, chronic low back pain, and musculoskeletal injuries)
• Contraindications/medically unfit to receive hyperbaric treatments at an outpatient facility (e.g. pneumothorax, in-patients, requiring infusions to maintain hemodynamics, active and unstable coronary disease)
• Unlikely to comply with follow-up assessments (e.g. no fixed address, plans to move out of town)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• Sunnybrook Health Sciences Centre — Toronto

Identifiers

NCT: NCT06579040 · 6201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗